Sunday, May 27, 2007

SCIENCE Questions: How Much Can Human Life Be Extended?

 
"How Much Can Human Life Be Extended?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...
Couzin, Jennifer (2005) How Much Can Human Life Be Extended? Science 309: 83.
[Text] [PDF]
Jennifer Couzin is a San Francisco-based news writer for Science magazine. She also wrote on "To What Extent Are Genetic Variation and Personal health Linked?".

With respect to the sort of fundamental questions that are described in the lead article [SCIENCE Questions: Asking the Right Question], this is a stupid question. It isn't really a science question at all; it's a question about technology, or the application of science. If a leading magazine like Science can't get the difference between technology and fundamental science questions then we're in a lot more trouble than I thought.

Compare this question to one of the valid questions that is asked, "What Is the Universe Made of?" Does anyone really think that a question about how to prolong human lifetimes is in the same category as a question about dark matter?

Not only is this not a "science" question, it's a question that reflects a huge bias in favor of a single species, Homo sapiens. If our goal is to teach science literacy then surely one of the most important ways to advance this goal is to convince people that there's a lot more to science than just it's interface with medicine. As long as the general public continues to treat science as a means to an end then we're never going to convince them that knowledge for its own sake is valuable.

10 comments :

  1. I think you're missing the point, Larry. Asking if there is upper theoretical limit to human lifespans is quite definitely a scientific question. Medicine and technology maybe could help humans reach the upper limit, but not really help us understand why (or if) there is such a limit.

    The evolutionary implications of senescence are, at least to me as a biologist, at least as interesting as questions about dark matter. Is it really just that the question was framed in terms of *human* life that bothered you? How about in terms of guppy life?

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  2. The problem I have with this question is that it doesn't really have an answer than can be known for logistic or for ethical reasons. It isn't really a "scientific" question.

    There are life extension methods that are objectionable, such as generating clones simply to harvest organs for transplant. Unless those methods are tried, we won't know the "scientific" answer to the question.

    There are methods which are possible (in principle) but which are extremely difficult (but not necessarily impossible) to actually implement. Such as designing a "human" "from scratch", putting all the DNA together and growing it into a "human". I have no doubt that with sufficient resources that this could be done, and the resulting "human" could have a virtually indefinite lifespan. You could make this "person" chimeric and replace the different cell lines periodically as needed with fresh stem cells that would migrate in and replace cell lines as they got "tired". It might take a few trillion person-years (or more?) to achieve, but I don't think there is anything inherently "impossible" about it. It is just so far beyond our present capabilities that it isn't useful to even think about a plan to do it. But until we know that there is some "show stopper" in that scheme, the "scientific question" of can it be done remains open.

    The answer to "scientific" questions should not be so methods dependent.

    It is a "gee whiz Mr. Scientist, what about this?" kind of question a non-scientist would ask. The objection to such questions being raised and taken seriously is that then the funding agencies start to take them seriously, and you have "scientists" speculating on what can be done in what time frame with what funding (as in SENS for example, $10 billion in 10 years) chasing chimera and achieving no real advancement in knowledge.

    People simply do not appreciate how complicated biological systems are. They seem "simple" because several billion years of evolution have made them "work". The mischaracterization of DNA sequencing as "decoding" is symptomatic of the lack of appreciation of how complicated it is. This lack of appreciation is not limited to non-scientists. The leader of the consortium that sequenced the honeybee genome Apis mellifera (George Weinstock) was asked "What was the biggest surprise about the bee's genome?" His answer: "That we did not come up with breakthroughs in understanding social behaviour of the bee. Many small changes account for this and it is possible that this reflects our limited knowledge of behavioural genetics." Yes and the difficulty of understanding systems of thousands of coupled non-linear parameters with feedback and hysteresis.

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  3. If you read what the article says (which is actually here, Larry having accidentally linked twice to the other Couzin article), you'll see the article isn't about organ harvesting or other dystopian fears of unethical pseudoscience but serious study behind the genetic mechanisms that are responsible for the observed extension of lifespans of other animals under calorie restriction.

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  4. I have to agree with Jonathan here. Whether or not there is a theoretical upper limit on human lifespan (or lifespans of organisms in general) is most definitely a valid scientific question. Just because a question could have a practical use in humans does not automatically make it a "practical" rather than scientific question.

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  5. I know they were not asking about organ harvesting. If you restrict the "answer" to "methods that are not objectionable", it isn't a "scientific" question any more, it becomes an ethical question. "How much can human life be extended using ethical methods". I am not saying we should use unethical methods, but if you limit the methods to what is "ethical" the limiting factor becomes what is our definition of "ethical". Casting the "question" in terms of interventions to extend life doesn't necessarily result in satisfaction once the "answer" is known.

    A better question would be "what causes senescence"? What are the physiological trade-offs between senescence, reproduction, infection prevention, growth, healing, etc, in the short and long term. The focus on life extension through calorie restriction is (I think), far too limited and short sighted. Each and every organism senesces. Each and every organism does so at different rates. Why those rates are different and by what mechanisms is (I think), a much better question.

    I think that a generic problem in this area is that there are fundamental misconceptions about physiology that are impeding progress. The most serious (I think), is the myth of homeostasis. I will send you a poster I presented on ATP hierarchies. It is my hypothesis that much of the degeneration that is observed is a consequence of low NO causing low ATP, which invokes ATP conservation (as in ischemic preconditioning). Ischemic preconditioning transiently reduces ATP consumption. Presumably, if there were no adverse effects, cells would have evolved to be in this state continuously. Presumably it involves putting off some ATP consuming tasks until later to conserve ATP for immediate consumption. Presumably those tasks are long time constant and turning them off only affects things in the long term. I think this is a major cause of senescence (if not the major cause) because these long term pathways are repair pathways. I think that "stimulants", transiently lower ATP concentration, which turns off the long time constant pathways, which frees up that ATP for immediate consumption (which is why they are stimulants). The degeneration associated with stimulant use is (I think) a consequence of that ATP reduction, and the turning off of long term repair pathways.

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  6. daedalus2u says,

    A better question would be "what causes senescence"?

    I agree.

    What are the physiological trade-offs between senescence, reproduction, infection prevention, growth, healing, etc, in the short and long term.

    No. That's too specific. We're interested in senescence in all species, including single-cell species.

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  7. Jonathan Badger asks,

    I think you're missing the point, Larry. Asking if there is upper theoretical limit to human lifespans is quite definitely a scientific question. Medicine and technology maybe could help humans reach the upper limit, but not really help us understand why (or if) there is such a limit.

    Studies on aging and senescence are legitimate pure science. Many of my colleagues are working on such problems using yeast and nematodes as model systems. I know of some excellent work on plants as well.

    An example of a good science question would be "What causes cells and organisms to die?"

    The evolutionary implications of senescence are, at least to me as a biologist, at least as interesting as questions about dark matter. Is it really just that the question was framed in terms of *human* life that bothered you? How about in terms of guppy life?

    Yes, it's the way the question is phrased that bothers me. When it's put like that it excludes from interest any studies on other organisms unless they contribute to extending human lifetimes. In other words, the way the question is worded make it seem like scientists aren't interested in the broader scientific aspect of senescence and aging but only in its application to humans.

    You should consider a general question on aging when I call for the science bloggers to contribute their questions. I think it's a good candidate even though I'm a bit skeptical about whether there's anything new to be discovered. (I favor the hypothesis that things just wear out over time.)

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  8. Larry, the trade-off of senescence vs. reproduction, infection prevention, growth, healing, etc, is not limited to multi-celled organisms. Presumably because there are different rates of senescence among different species there are different local "optima" that those organisms have reached. That there are differences even among clonal organisms indicates that the trade-offs are regulated (to some extent) by environmental effects.

    I think you are right that "things just wear out over time", but how much effort gets put into preventative maintenance has an effect on how long that takes. The apportionment of resources to repair and preventative maintenance is (I think) a major factor in how rapidly senescence occurs. That is the gist of my ATP hierarchies poster. "Repair", that is removing and replacing damaged proteins, damaged DNA, consumes ATP. Some of it can be put off until later if there is something more important to do (such as running from a bear). But put it off and the damage accumulates and interferes with the eventual repair. Put it off too long, and eventually repair becomes impossible and the system falls apart.

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  9. "Yes, it's the way the question is phrased that bothers me. When it's put like that it excludes from interest any studies on other organisms unless they contribute to extending human lifetimes."

    The rephrasing from "a question about technology, or the application of science" is better, but not much. This could be expanded to a long discussion about the worth of applied science, correlation between science and technology, and strategies of science such as the balance between pure and applied science and how to get expanded funding.

    But to cut it short now, applied science and restrictions of technology on science are a reality. [Disclaimer #1: I have only worked with applied science. So obviously I'm partial. :-)]

    It may be much more apparent in parts of physics, where research on transient technologies (such as variants of electronics) and limits of technology (such as accelerator physics) are common.

    One could say that biochemistry is applied science too - but the particular system happens to be persistent and reused. ;-)

    And IMHO where could be many interesting research topics in senescence. [Disclaimer #2: Both personally and socially I find this an interesting field. Why not?]

    The easy to understand concentration to quick fixes (current researchers may have a personal interest in the results) and the human interest (more funding) and its consequences (risk for loss of interest when high risk easy pickings doesn't pan out; pulling funding from other areas) could be discussed.

    But it is a much larger question which comes back again and again. It fits within the larger frame of the series of top questions in science though, so perhaps it is a discussion we should have at some point.

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  10. I reviewed Rose's The Long Tomorrow, which covers some senescence issues in a generally-accessible form - which means it can be a little bit plodding for those a bit more in the know, but it was informative nonetheless.

    What I thought was particularly interesting about the research were two observations: one, lifespan seems very reflective of and tied to reproduction. Repeated reproduction delays or sterilization increased lifespans for future generations or individuals, respectively. The more of an organism that is dedicated to reproduction, the more difference it seems to make. "Why?" is a damned fine question at this point.

    The other was that mortality rate does not technically hit 100%. Mortality does, but it's statistically-based. The percentage chance of dying on any given day at any given age in humans is high, but there is no guaranteed age you're going to die at. It's like rolling six dice a day and if you get all sixes, you die. Sure, it's possible that all sixes could never come up, but the statistician would be able to estimate how many people were living at any given age.

    Rose takes that as a good omen that it's a slope, not a wall, and we might even just be able to do something about the slope.

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